This proposal examines the neural mechanisms underlying action inhibition, which is the cancelation of an initiated motor response. Healthy adults exhibit flexible motor behavior whereas adults with Parkinson's disease (PD) experience difficulty inhibiting action. In particular, PD patients demonstrate a specific deficit turning off muscle activity. The goal of this mentored grant is twofold: 1) to develop a clear understanding about how brain activity, brain connectivity, and cognitive function are related to the cancelation of an initiated motor response in health and PD, and 2) to provide Dr. Neely with a foundation for a career as an independent biomedical research scientist. We will use a novel grip force inhibition paradigm wherein we will simultaneously measure grip force and blood-oxygen-level-dependent (BOLD) activity using functional magnetic resonance imaging (fMRI). We will pursue three specific aims. Aim 1 examines the BOLD signal and functional connectivity when grip force is inhibited in predictable versus unpredictable force amplitude conditions. Aim 2 examines the BOLD signal and functional connectivity when grip force is inhibited in high force versus low force amplitude conditions. Aim 3 examines the BOLD signal and functional connectivity when adults with early-stage PD inhibit predictable, moderate-amplitude grip force. In all three Aims, we will administer tests of cognitive function and trait impulsivity. The proposed work is significant because it increases our understanding of how brain activity and connectivity are altered by the predictability and amplitude of force output. Moreover, the research contributes to a greater understanding of how impaired action inhibition correlates with brain activity and connectivity in adults with PD. This research is innovative because we will examine how trait impulsivity and cognitive control correlate with behavioral performance, brain activity, and brain connectivity. Further, we will examine how disease severity in PD correlates with behavioral performance, brain activity, and brain connectivity. Such knowledge facilitates the development of surgical and pharmaceutical interventions that target specific cortical and subcortical areas related to inhibiting and/or stopping motor output. The outcomes of this research will motivate the next phase of Dr. Neely's research program, which is to understand how antiparkinson treatments such as deep brain stimulation and dopamine agonists alter the neural mechanisms underlying action inhibition. PUBLIC HEALTH RELEVANCE: This proposal examines the neural mechanisms underlying action inhibition. Action inhibition is the cancelation of an initiated motor response and is essential to many motor tasks. This research will contribute to an improved understanding of how the brain inhibits movement in healthy young adults and in adults with early-stage Parkinson's disease (PD). This is important because in addition to PD, impaired action inhibition is a characteristic of many neurological and neuropsychiatric disorders such as Huntington's disease, Tourette's syndrome, and schizophrenia.